title: Extended-release quetiapine fumarate (quetiapine XR) monotherapy and quetiapine XR or lithium as add-on to antidepressants in patients with treatment-resistant major depressive disorder.
abstract: BACKGROUND
  Patients with treatment-resistant major depressive disorder (MDD) remain a common clinical challenge.
  
  
  METHODS
  This 6-week, randomised, open-label, rater-blinded trial evaluated once-daily extended-release quetiapine fumarate (quetiapine XR; 300 mg/day) as add-on to ongoing antidepressant and quetiapine XR monotherapy (300 mg/day) compared with add-on lithium (0.6-1.2 mmol/L) in patients with treatment-resistant MDD. Primary efficacy measure: change in Montgomery Åsberg Depression Rating Scale (MADRS) total score from randomisation to week 6 with a pre-specified non-inferiority limit of 3 points on the MADRS.
  
  
  RESULTS
  At week 6, both add-on quetiapine XR (n=231) and quetiapine XR monotherapy (n=228) were non-inferior to add-on lithium (n=229); least squares means (LSM) differences (97.5% CI) in MADRS total score changes were -2.32 (-4.6, -0.05) and -0.97 (-3.24, 1.31), respectively. LSM MADRS total score change was numerically greater at day 4 for both quetiapine XR groups (add-on and monotherapy; p<0.01) compared with add-on lithium. At week 6, the differences between groups for the secondary endpoints of MADRS response (≥ 50% reduction in total score), MADRS remission (total score ≤ 10, add-on quetiapine XR only) and Clinical Global Impressions ('much'/'very much' improved) were numerically similar. Overall tolerability was consistent with the known profiles of both treatments.
  
  
  CONCLUSIONS
  Limitations included the open-label study design (although MADRS and laboratory measurements were performed by treatment-blinded raters) and relatively short study duration with no assessments in the continuation phase.
  
  
  CONCLUSIONS
  Add-on quetiapine XR (300 mg/day) and quetiapine XR monotherapy (300 mg/day) are non-inferior to add-on lithium in the management of patients with treatment-resistant MDD.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, D-01307 Dresden, Germany. Michael.Bauer@uniklinikum-dresden.de
authors.forename: Michael
authors.initials: M
authors.lastname: Bauer
authors.forename: Liliana
authors.initials: L
authors.lastname: Dell'osso
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
authors.forename: William
authors.initials: W
authors.lastname: Pitchot
authors.forename: Eva
authors.initials: E
authors.lastname: Dencker Vansvik
authors.forename: Jürgen
authors.initials: J
authors.lastname: Köhler
authors.forename: Leif
authors.initials: L
authors.lastname: Jørgensen
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Montgomery
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D003865:Major Depressive Disorder / Q000188:drug therapy*; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy*; D003987:Dibenzothiazepines / Q000008:administration & dosage* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008094:Lithium / Q000008:administration & dosage / Q000627:therapeutic use; D018020:Lithium Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D000069348:Quetiapine Fumarate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D003987:Dibenzothiazepines; D018020:Lithium Compounds; D000069348:Quetiapine Fumarate; D008094:Lithium
keywords: Atypical antipsychotic; Augmentation; Lithium; Major depressive disorder; Quetiapine XR; Treatment-resistant depression